国产与进口替米沙坦制剂在人体内的药动学及生物等效性

Pharmacokinetics and bioequivalence of domestic and imported telmisartan in healthy male volunteers

目的:建立人血浆中替米沙坦浓度的高效液相色谱-质谱(HPLC-MS)分析方法,评价国产和进口替米沙坦制剂的生物等效性。方法:采用随机交叉试验方法,用HPLC-MS法对国产替米沙坦胶囊和进口替米沙坦片在20名中国健康男性受试者中的血药浓度进行测定。药动学参数用3P97程序进行计算。结果:国产与进口替米沙坦制剂的AUC_(0～t)分别是:(1 861±s 198)和(1 833±186)μg·h·L^(-1);c_(max)为(181±36)和(180±32)μg·L^(-1);t_(1/2)为(18.8±2.9)和(19±3)h。国产替米沙坦胶囊的相对生物利用度为(104±19)%。AUC_(0～t)、c_(max)经对数转换后方差分析和t检验表明两制剂生物等效。结论:HPLC-MS法测定替米沙坦简便,准确,灵敏度高。国产替米沙坦胶囊和进口替米沙坦片具有生物等效性。

[ABSTRACT] AIM ： of telmisartan in human. To establish a HPLC-MS method for the study of METHODS： A randomized crossover design pharmacokinetics and bioequivalence was performed in 20 healthy male volunteers. In the two study periods, a single 40 mg dose of each capsule or tablet was administered to each volunteer. The plasma concentration was determined by HPLC-MS method, and the pharmacokinetic parameters were calculated by the pharmacokinetic program 3P97. RESULTS： A UC0-1 of telmisartan for the test and reference preparations were （1 861 ± s 198） and （1 833± 186）μg·h·L^-1, Cmax were （181 ± 36） and （180 ± 32）μg·h·L^-1, t1/2 were （ 18.8±2.9） and （ 19 ± 3） h, respectively. The relative bioavailability of the test preparation was （104 ±19） %. Bioequivalence results on logarithmic transformations of AUC0-t and Cmax were calculated by analysis of variance, t test and the results showed that the two preparations were bioequivalent. CONCLUSION： HPLC-MS method is sensitive, accurate and convenient for the determination of telmisartan. The domestic and imported telmisartan are bioequivalent.